Various normal and malignant mouse tissue endopoints will be used to investigate the efficacy of combining certain drugs with radiation for the treatment of cancer. The endpoints which will be used will be, for tumors: cell survival curves using both in situ and in vitro irradiation, delay in regrowth and tumor cure; and for normal tissues: early and late reactions in the irradiated leg, radiation pneumonitis, radiation myelitis and radiation nephritis. In addition, the rabbit will be investigated as a possible model for the characteristic veno- occlusive radiation hepatitis lesion seen in humans. The drugs to be used will be first, the pyrimidine analog 5-bromo- 2'-deoxycytidine (BCdR), which will be investigated both from the point of its ability to sensitize lung metastases by i.v. infusion and for its ability to sensitize solid tumors when combined with an agent which will block it deamination in vivo. Second, the ability of the drugs metronidazole and RO7-0582 to sensitize only hypoxic cells to irradiation will be investigated in single and multiple fraction dose protocols. Third, the anticoagulant warfarin will be used to determine whether any of the late effects of irradiation--particularly radiation hepatitis--can be lessened or prevented following its administration. The undersigned agrees to accept responsibility for the scientific and technical conduct of the project and for provision of required progress reports if a grant is awarded as the result of this application.